The objectives of the proposed research are to evaluate the role of various systems involved in control of water excretion in health and disease states. More specifically, both in vitro and in vivo experiments will be carried out to evaluate: 1) the effect the catecholamines, prostaglandins and angiotensin II on release of ADH, 2) examine the mechanisms underlying abnormal water excretion in disturbances of thyroid gland function, 3) study the mechanisms of disturbances of water excretion of the glucocorticoid deficient state, 4) study the effects of thyroid hormone excess and deficiency and of cortisol deficiency on responses of renal medullary cyclic AMP to ADH and other agonists, as well as the response of other enzymatic processes (i.e. cortical cyclic AMP, gluconeogenesis) to various hormones and agonists, 5) evaluate the mechanisms involved in renal resistance to ADH after relief of ureteral obstruction, 6) evaluate the cellular mechanisms involved in the renal resistance to ADH during hypercalcemia or potassium deficiency, 7) explore the role of prostaglandins in the various states of abnormal water excretion and 8) study the distribution of cyclic AMP and GMP in renal cells. The results may help to understand the basic mechanisms modulating the renal excretion and may provide a basis for the management of various syndromes with abnormalities of water excretion.